Measurements of levels of 17α-OHP are useful in the evaluation of patients with suspected congenital adrenal hyperplasia as the typical enzymes that are defective, namely 21-hydroxylase and 11β-hydroxylase, lead to a build-up of 17α-OHP. In contrast, the rare patient with 17α-hydroxylase deficiency will have very low or undetectable levels of 17α-OHP. 17α-OHP levels can also be used to measure contribution of progestational activity of the corpus luteum during pregnancy as progesterone but not 17α-OHP is also contributed by the placenta.

1.
Hydroxyprogesterone caproate
–
It is an ester of 17α-OHP formed from caproic acid. OHPC was previously marketed under the trade name Delalutin by Squibb and it is also sold as Proluton throughout Europe. The U. S. FDA approved Makena from KV Pharmaceutical on February 4,2011 for prevention of preterm delivery in women with a history of preterm delivery, sparking a pricing controversy. It was used widely in the 1950s through the 1970s for these indications, OHPC250 mg IM weekly preferably starting at 16–20 weeks until 36 weeks is recommended. In these women, if the transvaginal ultrasound cervical length shortens to <25 mm at <24 weeks, furthermore, this study contained 463 patients,310 of whom received injection. Of these patients,9 had infants with congenital malformations, but there was no consistent pattern, OHPC is currently pregnancy category B, meaning there is no evidence of fetal risk with use of this drug during pregnancy. Although this is now the recommendation, this has not always been the case, a 2006 Cochrane Review concluded. important maternal and infant outcomes have been poorly reported to date. Information regarding the potential harms of progesterone therapy to prevent preterm birth is limited, there was a similar conclusion from a review by Marc Keirse of Flinders University. Three clinical studies in singleton pregnancies of 250 mg/week of intramuscular OHPC have all shown a trend for an increase in pregnancy due to miscarriage compared to placebo. A follow-up study of the offspring showed no evidence that OHPC affected the children in the first years of life, based on these NIH data,17 OHPC was approved by the FDA in 2011 as a drug to reduce the risk of premature birth in selected patients at risk. There is speculation that the oil in the OHPC formulation may not be beneficial for pregnancy. Of note, the above-mentioned NEJM study by Meirs et al. compares the effect of OHPC to castor oil injection as the placebo and this story is ended, and nobody need ever use vaginal progesterone again to prevent preterm birth. OHPC is significantly effective in extending life in both premenopausal and postmenopausal women with advanced endometrial cancer, OHPC is used as a component of hormone replacement therapy for transgender women. OHPC has been used to treat benign prostatic hyperplasia in men, although evidence of effectiveness is marginal, however, symptoms of hypogonadism may develop when OHPC is used for this indication, with two-thirds of men reportedly experiencing impotence. However, relative to progesterone, OHPC has improved pharmacokinetics, namely, via intramuscular injection,250 mg OHPC is said to be equivalent to 50 mg of medroxyprogesterone acetate. Through activation of the PR, OHPC has the potential for marked antigonadotropic effects, as a pure progestogen, OHPC has no androgenic or glucocorticoid properties, nor any estrogenic effects. Due to its lack of androgenic properties, similarly to progesterone, OHPC does not have any effects on the fetus. OHPC has been studied in humans at dosages as high as 5,000 mg per week via intramuscular injection, in animals, the bioavailability of OHPC with intramuscular injection is nearly 100%, but its oral bioavailability is very low at less than 3%

2.
Hydroxyprogesterone acetate
–
OHPA is a progestogen and acts as an agonist of the progesterone receptor, both PRA and PRB isoforms. It has far higher affinity for the PR isoforms than 17α-hydroxyprogesterone, a less than half the affinity of progesterone. OHPA is of low potency as a progestogen, which may explain its limited relative use. It is 100-fold less potent than medroxyprogesterone acetate, 400-fold less potent than chlormadinone acetate, OHPA also is reportedly more potent than OHPC. Along with OHPC, OHPA was synthesized by Karl Junkmann of Schering AG in 1953 and was first reported by him in the literature in 1954. OHPC shows very low activity and was introduced for use via intramuscular injection by Squibb in 1956 under the brand name Delalutin. OHPA was found to two to three times the oral activity of 17α-methylprogesterone. Upjohn reported the oral activity of OHPA in the literature in 1957. In 1960, OHPA was introduced as Prodox as an oral progestin for veterinary use for the indication of estrus suppression in dogs, however, probably due its high cost and the inconvenience of daily oral administration, the drug was not a market success. Hydroxyprogesterone caproate Hydroxyprogesterone heptanoate Algestone acetophenide

3.
Jmol
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Jmol is computer software for molecular modelling chemical structures in 3-dimensions. Jmol returns a 3D representation of a molecule that may be used as a teaching tool and it is written in the programming language Java, so it can run on the operating systems Windows, macOS, Linux, and Unix, if Java is installed. It is free and open-source software released under a GNU Lesser General Public License version 2.0, a standalone application and a software development kit exist that can be integrated into other Java applications, such as Bioclipse and Taverna. A popular feature is an applet that can be integrated into web pages to display molecules in a variety of ways, for example, molecules can be displayed as ball-and-stick models, space-filling models, ribbon diagrams, etc. Jmol supports a range of chemical file formats, including Protein Data Bank, Crystallographic Information File, MDL Molfile. There is also a JavaScript-only version, JSmol, that can be used on computers with no Java, the Jmol applet, among other abilities, offers an alternative to the Chime plug-in, which is no longer under active development. While Jmol has many features that Chime lacks, it does not claim to reproduce all Chime functions, most notably, Chime requires plug-in installation and Internet Explorer 6.0 or Firefox 2.0 on Microsoft Windows, or Netscape Communicator 4.8 on Mac OS9. Jmol requires Java installation and operates on a variety of platforms. For example, Jmol is fully functional in Mozilla Firefox, Internet Explorer, Opera, Google Chrome, fast and Scriptable Molecular Graphics in Web Browsers without Java3D

4.
ChEMBL
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ChEMBL or ChEMBLdb is a manually curated chemical database of bioactive molecules with drug-like properties. It is maintained by the European Bioinformatics Institute, of the European Molecular Biology Laboratory, based at the Wellcome Trust Genome Campus, Hinxton, the database, originally known as StARlite, was developed by a biotechnology company called Inpharmatica Ltd. later acquired by Galapagos NV. The data was acquired for EMBL in 2008 with an award from The Wellcome Trust, resulting in the creation of the ChEMBL chemogenomics group at EMBL-EBI, the ChEMBL database contains compound bioactivity data against drug targets. Bioactivity is reported in Ki, Kd, IC50, and EC50, data can be filtered and analyzed to develop compound screening libraries for lead identification during drug discovery. ChEMBL version 2 was launched in January 2010, including 2.4 million bioassay measurements covering 622,824 compounds and this was obtained from curating over 34,000 publications across twelve medicinal chemistry journals. ChEMBLs coverage of available bioactivity data has grown to become the most comprehensive ever seen in a public database, in October 2010 ChEMBL version 8 was launched, with over 2.97 million bioassay measurements covering 636,269 compounds. ChEMBL_10 saw the addition of the PubChem confirmatory assays, in order to integrate data that is comparable to the type, ChEMBLdb can be accessed via a web interface or downloaded by File Transfer Protocol. It is formatted in a manner amenable to computerized data mining, ChEMBL is also integrated into other large-scale chemistry resources, including PubChem and the ChemSpider system of the Royal Society of Chemistry. In addition to the database, the ChEMBL group have developed tools and these include Kinase SARfari, an integrated chemogenomics workbench focussed on kinases. The system incorporates and links sequence, structure, compounds and screening data, the primary purpose of ChEMBL-NTD is to provide a freely accessible and permanent archive and distribution centre for deposited data. July 2012 saw the release of a new data service, sponsored by the Medicines for Malaria Venture. The data in this service includes compounds from the Malaria Box screening set, myChEMBL, the ChEMBL virtual machine, was released in October 2013 to allow users to access a complete and free, easy-to-install cheminformatics infrastructure. In December 2013, the operations of the SureChem patent informatics database were transferred to EMBL-EBI, in a portmanteau, SureChem was renamed SureChEMBL. 2014 saw the introduction of the new resource ADME SARfari - a tool for predicting and comparing cross-species ADME targets

5.
ChemSpider
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ChemSpider is a database of chemicals. ChemSpider is owned by the Royal Society of Chemistry, the database contains information on more than 50 million molecules from over 500 data sources including, Each chemical is given a unique identifier, which forms part of a corresponding URL. This is an approach to develop an online chemistry database. The search can be used to widen or restrict already found results, structure searching on mobile devices can be done using free apps for iOS and for the Android. The ChemSpider database has been used in combination with text mining as the basis of document markup. The result is a system between chemistry documents and information look-up via ChemSpider into over 150 data sources. ChemSpider was acquired by the Royal Society of Chemistry in May,2009, prior to the acquisition by RSC, ChemSpider was controlled by a private corporation, ChemZoo Inc. The system was first launched in March 2007 in a release form. ChemSpider has expanded the generic support of a database to include support of the Wikipedia chemical structure collection via their WiChempedia implementation. A number of services are available online. SyntheticPages is an interactive database of synthetic chemistry procedures operated by the Royal Society of Chemistry. Users submit synthetic procedures which they have conducted themselves for publication on the site and these procedures may be original works, but they are more often based on literature reactions. Citations to the published procedure are made where appropriate. They are checked by an editor before posting. The pages do not undergo formal peer-review like a journal article. The comments are moderated by scientific editors. The intention is to collect practical experience of how to conduct useful chemical synthesis in the lab, while experimental methods published in an ordinary academic journal are listed formally and concisely, the procedures in ChemSpider SyntheticPages are given with more practical detail. Comments by submitters are included as well, other publications with comparable amounts of detail include Organic Syntheses and Inorganic Syntheses

6.
European Chemicals Agency
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ECHA is the driving force among regulatory authorities in implementing the EUs chemicals legislation. ECHA helps companies to comply with the legislation, advances the safe use of chemicals, provides information on chemicals and it is located in Helsinki, Finland. The Agency, headed by Executive Director Geert Dancet, started working on 1 June 2007, the REACH Regulation requires companies to provide information on the hazards, risks and safe use of chemical substances that they manufacture or import. Companies register this information with ECHA and it is freely available on their website. So far, thousands of the most hazardous and the most commonly used substances have been registered, the information is technical but gives detail on the impact of each chemical on people and the environment. This also gives European consumers the right to ask whether the goods they buy contain dangerous substances. The Classification, Labelling and Packaging Regulation introduces a globally harmonised system for classifying and labelling chemicals into the EU. This worldwide system makes it easier for workers and consumers to know the effects of chemicals, companies need to notify ECHA of the classification and labelling of their chemicals. So far, ECHA has received over 5 million notifications for more than 100000 substances, the information is freely available on their website. Consumers can check chemicals in the products they use, Biocidal products include, for example, insect repellents and disinfectants used in hospitals. The Biocidal Products Regulation ensures that there is information about these products so that consumers can use them safely. ECHA is responsible for implementing the regulation, the law on Prior Informed Consent sets guidelines for the export and import of hazardous chemicals. Through this mechanism, countries due to hazardous chemicals are informed in advance and have the possibility of rejecting their import. Substances that may have effects on human health and the environment are identified as Substances of Very High Concern 1. These are mainly substances which cause cancer, mutation or are toxic to reproduction as well as substances which persist in the body or the environment, other substances considered as SVHCs include, for example, endocrine disrupting chemicals. Companies manufacturing or importing articles containing these substances in a concentration above 0 and they are required to inform users about the presence of the substance and therefore how to use it safely. Consumers have the right to ask the retailer whether these substances are present in the products they buy, once a substance has been officially identified in the EU as being of very high concern, it will be added to a list. This list is available on ECHA’s website and shows consumers and industry which chemicals are identified as SVHCs, Substances placed on the Candidate List can then move to another list

7.
IUPHAR/BPS
–
The IUPHAR/BPS Guide to PHARMACOLOGY is an open-access website, acting as a portal to information on the biological targets of licensed drugs and other small molecules. The Guide to PHARMACOLOGY is developed as a joint venture between the International Union of Basic and Clinical Pharmacology and the British Pharmacological Society and this replaces and expands upon the original 2009 IUPHAR Database. The information featured includes pharmacological data, target and gene nomenclature, overviews and commentaries on each target family are included, with links to key references. The Guide to PHARMACOLOGY was initially made available online in December 2011 with additional material released in July 2012 and its network of over 700 specialist advisors contribute expertise and data. The current PI and Grant holder of the GtoPdb project is Prof. Jamie A. Davies, the development and release of the first version of the GtoPdb in 2012 was described in an editorial published in the British Journal of Pharmacology entitled Guide to Pharmacology. org- an update. The IUPHAR-DB is no longer being developed and all the contained within this site is now available through the Guide to PHARMACOLOGY. A complete list of all the approved drugs included on the website is available via the ligand list. The Guide to PHARMACOLOGY is being expanded to include information on targets and ligands. Search features on the website include quick and advanced search options, other features include Hot topic news items and a recent receptor-ligand pairing list. A hard copy summary of the database is published as The Concise Guide to Pharmacology 2015/2016 as a series of papers as a bi-annual supplement to the British Journal of Pharmacology. The Guide to PHARMACOLOGY includes links to other relevant resources via target, many of these resources maintain reciprocal links with the relevant Guide to PHARMACOLOGY pages. As of November 2015 the Wellcome Trust is supporting a new project to develop the Guide to Immumopharmacology, the latter continues to be supported by the British Pharmacological Society

8.
PubChem
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PubChem is a database of chemical molecules and their activities against biological assays. The system is maintained by the National Center for Biotechnology Information, a component of the National Library of Medicine, PubChem can be accessed for free through a web user interface. Millions of compound structures and descriptive datasets can be downloaded via FTP. PubChem contains substance descriptions and small molecules with fewer than 1000 atoms and 1000 bonds, more than 80 database vendors contribute to the growing PubChem database. PubChem consists of three dynamically growing primary databases, as of 28 January 2016, Compounds,82.6 million entries, contains pure and characterized chemical compounds. Substances,198 million entries, contains also mixtures, extracts, complexes, bioAssay, bioactivity results from 1.1 million high-throughput screening programs with several million values. PubChem contains its own online molecule editor with SMILES/SMARTS and InChI support that allows the import and export of all common chemical file formats to search for structures and fragments. In the text search form the database fields can be searched by adding the name in square brackets to the search term. A numeric range is represented by two separated by a colon. The search terms and field names are case-insensitive, parentheses and the logical operators AND, OR, and NOT can be used. AND is assumed if no operator is used, example,0,5000,50,10 -5,5 PubChem was released in 2004. The American Chemical Society has raised concerns about the publicly supported PubChem database and they have a strong interest in the issue since the Chemical Abstracts Service generates a large percentage of the societys revenue. To advocate their position against the PubChem database, ACS has actively lobbied the US Congress, soon after PubChems creation, the American Chemical Society lobbied U. S. Congress to restrict the operation of PubChem, which they asserted competes with their Chemical Abstracts Service

9.
International Chemical Identifier
–
Initially developed by IUPAC and NIST from 2000 to 2005, the format and algorithms are non-proprietary. The continuing development of the standard has supported since 2010 by the not-for-profit InChI Trust. The current version is 1.04 and was released in September 2011, prior to 1.04, the software was freely available under the open source LGPL license, but it now uses a custom license called IUPAC-InChI Trust License. Not all layers have to be provided, for instance, the layer can be omitted if that type of information is not relevant to the particular application. InChIs can thus be seen as akin to a general and extremely formalized version of IUPAC names and they can express more information than the simpler SMILES notation and differ in that every structure has a unique InChI string, which is important in database applications. Information about the 3-dimensional coordinates of atoms is not represented in InChI, the InChI algorithm converts input structural information into a unique InChI identifier in a three-step process, normalization, canonicalization, and serialization. The InChIKey, sometimes referred to as a hashed InChI, is a fixed length condensed digital representation of the InChI that is not human-understandable. The InChIKey specification was released in September 2007 in order to facilitate web searches for chemical compounds and it should be noted that, unlike the InChI, the InChIKey is not unique, though collisions can be calculated to be very rare, they happen. In January 2009 the final 1.02 version of the InChI software was released and this provided a means to generate so called standard InChI, which does not allow for user selectable options in dealing with the stereochemistry and tautomeric layers of the InChI string. The standard InChIKey is then the hashed version of the standard InChI string, the standard InChI will simplify comparison of InChI strings and keys generated by different groups, and subsequently accessed via diverse sources such as databases and web resources. Every InChI starts with the string InChI= followed by the version number and this is followed by the letter S for standard InChIs. The remaining information is structured as a sequence of layers and sub-layers, the layers and sub-layers are separated by the delimiter / and start with a characteristic prefix letter. The six layers with important sublayers are, Main layer Chemical formula and this is the only sublayer that must occur in every InChI. The atoms in the formula are numbered in sequence, this sublayer describes which atoms are connected by bonds to which other ones. Describes how many hydrogen atoms are connected to each of the other atoms, the condensed,27 character standard InChIKey is a hashed version of the full standard InChI, designed to allow for easy web searches of chemical compounds. Most chemical structures on the Web up to 2007 have been represented as GIF files, the full InChI turned out to be too lengthy for easy searching, and therefore the InChIKey was developed. With all databases currently having below 50 million structures, such duplication appears unlikely at present, a recent study more extensively studies the collision rate finding that the experimental collision rate is in agreement with the theoretical expectations. Example, Morphine has the structure shown on the right, as the InChI cannot be reconstructed from the InChIKey, an InChIKey always needs to be linked to the original InChI to get back to the original structure

10.
Simplified molecular-input line-entry system
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The simplified molecular-input line-entry system is a specification in form of a line notation for describing the structure of chemical species using short ASCII strings. SMILES strings can be imported by most molecule editors for conversion back into two-dimensional drawings or three-dimensional models of the molecules, the original SMILES specification was initiated in the 1980s. It has since modified and extended. In 2007, a standard called OpenSMILES was developed in the open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, the original SMILES specification was initiated by David Weininger at the USEPA Mid-Continent Ecology Division Laboratory in Duluth in the 1980s. The Environmental Protection Agency funded the project to develop SMILES. It has since modified and extended by others, most notably by Daylight Chemical Information Systems. In 2007, a standard called OpenSMILES was developed by the Blue Obelisk open-source chemistry community. Other linear notations include the Wiswesser Line Notation, ROSDAL and SLN, in July 2006, the IUPAC introduced the InChI as a standard for formula representation. SMILES is generally considered to have the advantage of being slightly more human-readable than InChI, the term SMILES refers to a line notation for encoding molecular structures and specific instances should strictly be called SMILES strings. However, the term SMILES is also used to refer to both a single SMILES string and a number of SMILES strings, the exact meaning is usually apparent from the context. The terms canonical and isomeric can lead to confusion when applied to SMILES. The terms describe different attributes of SMILES strings and are not mutually exclusive, typically, a number of equally valid SMILES strings can be written for a molecule. For example, CCO, OCC and CC all specify the structure of ethanol, algorithms have been developed to generate the same SMILES string for a given molecule, of the many possible strings, these algorithms choose only one of them. This SMILES is unique for each structure, although dependent on the algorithm used to generate it. These algorithms first convert the SMILES to a representation of the molecular structure. A common application of canonical SMILES is indexing and ensuring uniqueness of molecules in a database, there is currently no systematic comparison across commercial software to test if such flaws exist in those packages. SMILES notation allows the specification of configuration at tetrahedral centers, and these are structural features that cannot be specified by connectivity alone and SMILES which encode this information are termed isomeric SMILES

11.
Chemical formula
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These are limited to a single typographic line of symbols, which may include subscripts and superscripts. A chemical formula is not a name, and it contains no words. Although a chemical formula may imply certain simple chemical structures, it is not the same as a full chemical structural formula. Chemical formulas can fully specify the structure of only the simplest of molecules and chemical substances, the simplest types of chemical formulas are called empirical formulas, which use letters and numbers indicating the numerical proportions of atoms of each type. Molecular formulas indicate the numbers of each type of atom in a molecule. For example, the formula for glucose is CH2O, while its molecular formula is C6H12O6. This is possible if the relevant bonding is easy to show in one dimension, an example is the condensed molecular/chemical formula for ethanol, which is CH3-CH2-OH or CH3CH2OH. For reasons of structural complexity, there is no condensed chemical formula that specifies glucose, chemical formulas may be used in chemical equations to describe chemical reactions and other chemical transformations, such as the dissolving of ionic compounds into solution. A chemical formula identifies each constituent element by its chemical symbol, in empirical formulas, these proportions begin with a key element and then assign numbers of atoms of the other elements in the compound, as ratios to the key element. For molecular compounds, these numbers can all be expressed as whole numbers. For example, the formula of ethanol may be written C2H6O because the molecules of ethanol all contain two carbon atoms, six hydrogen atoms, and one oxygen atom. Some types of compounds, however, cannot be written with entirely whole-number empirical formulas. An example is boron carbide, whose formula of CBn is a variable non-whole number ratio with n ranging from over 4 to more than 6.5. When the chemical compound of the consists of simple molecules. These types of formulas are known as molecular formulas and condensed formulas. A molecular formula enumerates the number of atoms to reflect those in the molecule, so that the formula for glucose is C6H12O6 rather than the glucose empirical formula. However, except for very simple substances, molecular chemical formulas lack needed structural information, for simple molecules, a condensed formula is a type of chemical formula that may fully imply a correct structural formula. For example, ethanol may be represented by the chemical formula CH3CH2OH

12.
Melting point
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The melting point of a solid is the temperature at which it changes state from solid to liquid at atmospheric pressure. At the melting point the solid and liquid phase exist in equilibrium, the melting point of a substance depends on pressure and is usually specified at standard pressure. When considered as the temperature of the change from liquid to solid. Because of the ability of some substances to supercool, the point is not considered as a characteristic property of a substance. For most substances, melting and freezing points are approximately equal, for example, the melting point and freezing point of mercury is 234.32 kelvins. However, certain substances possess differing solid-liquid transition temperatures, for example, agar melts at 85 °C and solidifies from 31 °C to 40 °C, such direction dependence is known as hysteresis. The melting point of ice at 1 atmosphere of pressure is close to 0 °C. In the presence of nucleating substances the freezing point of water is the same as the melting point, the chemical element with the highest melting point is tungsten, at 3687 K, this property makes tungsten excellent for use as filaments in light bulbs. Many laboratory techniques exist for the determination of melting points, a Kofler bench is a metal strip with a temperature gradient. Any substance can be placed on a section of the strip revealing its thermal behaviour at the temperature at that point, differential scanning calorimetry gives information on melting point together with its enthalpy of fusion. A basic melting point apparatus for the analysis of crystalline solids consists of an oil bath with a transparent window, the several grains of a solid are placed in a thin glass tube and partially immersed in the oil bath. The oil bath is heated and with the aid of the melting of the individual crystals at a certain temperature can be observed. In large/small devices, the sample is placed in a heating block, the measurement can also be made continuously with an operating process. For instance, oil refineries measure the point of diesel fuel online, meaning that the sample is taken from the process. This allows for more frequent measurements as the sample does not have to be manually collected, for refractory materials the extremely high melting point may be determined by heating the material in a black body furnace and measuring the black-body temperature with an optical pyrometer. For the highest melting materials, this may require extrapolation by several hundred degrees, the spectral radiance from an incandescent body is known to be a function of its temperature. An optical pyrometer matches the radiance of a body under study to the radiance of a source that has been previously calibrated as a function of temperature, in this way, the measurement of the absolute magnitude of the intensity of radiation is unnecessary. However, known temperatures must be used to determine the calibration of the pyrometer, for temperatures above the calibration range of the source, an extrapolation technique must be employed

13.
Progestogen
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Progestogens, also sometimes spelled progestagens or gestagens, are a class of steroid hormones that bind to and activate the progesterone receptor. Progesterone is the major and most important progestogen in the body, major examples of progestins include the 17α-hydroxyprogesterone derivative medroxyprogesterone acetate and the 19-nortestosterone derivative norethisterone. The progestogens are named for their function in maintaining pregnancy, although they are present at other phases of the estrous. They are one of three types of sex hormones, the others being estrogens like estradiol and androgens/anabolic steroids like testosterone. The progestogens are one of the five classes of steroid hormones, in addition to the androgens, estrogens, glucocorticoids. All endogenous progestogens are characterized by their basic 21-carbon skeleton, called a pregnane skeleton, in similar manner, the estrogens possess an estrane skeleton, and androgens, an androstane skeleton. The terms progesterone, progestogen, and progestin are mistakenly used interchangeably both in the literature and in clinical settings. While the progestins are structural analogues of progesterone, they are not functional analogues, the most important progestogen in the body is progesterone. Other endogenous progestogens include 16α-hydroxyprogesterone, 17α-hydroxyprogesterone, 20α-dihydroprogesterone, 5α-dihydroprogesterone, 11-deoxycorticosterone, progesterone is produced from cholesterol with pregnenolone as a metabolic intermediate. In the first step in the pathway, cholesterol is converted into pregnenolone]]. Thus, many tissues producing steroids, including the adrenal glands, testes, in some tissues, the enzymes required for the final product are not all located in a single cell. For example, in ovarian follicles, cholesterol is converted to androstenedione, an androgen, in the theca cells, fetal adrenal glands also produce pregnenolone in some species, which is converted into progesterone and estrogens by the placenta. In the human, the fetal adrenals produce dehydroepiandrosterone via the pregnenolone pathway, progesterone is the major progestogen produced by the corpus luteum of the ovary in all mammalian species. Luteal cells possess the enzymes to convert cholesterol to pregnenolone. Progesterone is highest in the phase of the estrous cycle. The role of the placenta in progestogen production varies by species, in the sheep, horse, and human, the placenta takes over the majority of progestogen production, whereas in other species the corpus luteum remains the primary source of progestogens. In the sheep and human, progesterone is the major placental progestogen, the equine placenta produces a variety of progestogens, primarily 5α-dihydroprogesterone and 5α, 20α-tetrahydroprogesterone, beginning on day 60. A complete luteo-placental shift occurs by day 120–150, comparison of progestogens List of steroidal progestogens List of progestogens available in the United States Utian WH, Shoupe D, Bachmann G, Pinkerton JV, Pickar JH

14.
Steroid hormone
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A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes, corticosteroids and sex steroids, within those two classes are five types according to the receptors to which they bind, glucocorticoids, mineralocorticoids, androgens, estrogens, and progestogens. Vitamin D derivatives are a closely related hormone system with homologous receptors. They have some of the characteristics of true steroids as receptor ligands, Steroid hormones help control metabolism, inflammation, immune functions, salt and water balance, development of sexual characteristics, and the ability to withstand illness and injury. The term steroid describes both hormones produced by the body and artificially produced medications that duplicate the action for the naturally occurring steroids, the natural steroid hormones are generally synthesized from cholesterol in the gonads and adrenal glands. These forms of hormones are lipids and they can pass through the cell membrane as they are fat-soluble, and then bind to steroid hormone receptors to bring about changes within the cell. Steroid hormones are generally carried in the blood, bound to specific carrier proteins such as sex hormone-binding globulin or corticosteroid-binding globulin, further conversions and catabolism occurs in the liver, in other peripheral tissues, and in the target tissues. A variety of synthetic steroids and sterols have also been contrived, most are steroids, but some non-steroidal molecules can interact with the steroid receptors because of a similarity of shape. Some synthetic steroids are weaker or stronger than the natural steroids whose receptors they activate, some examples are sex hormone-binding globulin, corticosteroid-binding globulin, and albumin. Most studies say that hormones can affect cells when they are not bound by serum proteins. This idea is known as the free hormone hypothesis and this idea is shown in Figure 1 to the right. One study has found that these complexes are bound by megalin, a membrane receptor. The hormone then follows a pathway of action. This process is shown in Figure 2 to the right, the role of endocytosis in steroid hormone transport is not well understood and is under further investigation. In order for steroid hormones to cross the lipid bilayer of cells they must overcome barriers that would prevent their entering or exiting the membrane. Gibbs free energy is an important concept here and these hormones, which are all derived from cholesterol, have hydrophilic functional groups at either end and hydrophobic carbon backbones. These energy barriers and wells are reversed for hormones exiting membranes, Steroid hormones easily enter and exit the membrane at physiologic conditions. They have been shown experimentally to cross membranes near a rate of 20 μm/s, though it is energetically more favorable for hormones to be in the membrane than in the ECF or ICF, they do in fact leave the membrane once they have entered it

15.
Biosynthesis
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Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds and this process often consists of metabolic pathways. Some of these pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these pathways include the production of lipid membrane components. The prerequisite elements for biosynthesis include, precursor compounds, chemical energy and these elements create monomers, the building blocks for macromolecules. Biosynthesis occurs due to a series of chemical reactions, for these reactions to take place, the following elements are necessary, Precursor compounds, these compounds are the starting molecules or substrates in a reaction. These may also be viewed as the reactants in a chemical process. Chemical energy, chemical energy can be found in the form of high energy molecules and these molecules are required for energetically unfavorable reactions. Furthermore, the hydrolysis of these compounds drives a reaction forward, high energy molecules, such as ATP, have three phosphates. Often, the phosphate is split off during hydrolysis and transferred to another molecule. Catalytic enzymes, these molecules are special proteins that catalyze a reaction by increasing the rate of the reaction, coenzymes or cofactors, cofactors are molecules that assist in chemical reactions. These may be metal ions, vitamin derivatives such as NADH and acetyl CoA, in the case of NADH, the molecule transfers a hydrogen, whereas acetyl CoA transfers an acetyl group, and ATP transfers a phosphate. Two examples of type of reaction occur during the formation of nucleic acids. For some of these steps, chemical energy is required, Precursor molecule + ATP ↽ − − ⇀ product AMP + PP i Simple compounds that are converted into other compounds with the assistance of cofactors. For example, the synthesis of phospholipids requires acetyl CoA, while the synthesis of another component, shingolipids. The general equation for these examples is, Precursor molecule + Cofactor → e n z y m e macromolecule Simple compounds that join together to create a macromolecule, for example, fatty acids join together to form phopspholipids. In turn, phospholipids and cholesterol interact noncovalently in order to form the lipid bilayer and this reaction may be depicted as follows, Molecule 1 + Molecule 2 ⟶ macromolecule Many intricate macromolecules are synthesized in a pattern of simple, repeated structures. For example, the simplest structures of lipids are fatty acids, fatty acids are hydrocarbon derivatives, they contain a carboxyl group “head” and a hydrocarbon chain “tail. ”These fatty acids create larger components, which in turn incorporate noncovalent interactions to form the lipid bilayer

16.
Androgen
–
This includes the activity of the primary male sex organs and development of male secondary sex characteristics. Androgens were first discovered in 1936, androgens increase in both boys and girls during puberty. Androgens are also the original anabolic steroids and the precursor of all estrogens, the primary and most well-known androgen is testosterone. Dihydrotestosterone and androstenedione are less known generally, but are of importance in male development. DHT in the embryo life causes differentiation of penis, scrotum, later in life DHT contributes to balding, prostate growth and sebaceous gland activity. Although androgens are described as sex hormones, both males and females have them to varying degrees, as is also true of estrogens. They are one of three types of sex hormones, the others being estrogens like estradiol and progestogens like progesterone, the main subset of androgens, known as adrenal androgens, is composed of 19-carbon steroids synthesized in the zona reticularis, the innermost layer of the adrenal cortex. Adrenal androgens function as weak steroids, and the subset includes dehydroepiandrosterone, dehydroepiandrosterone sulfate, androstenedione, besides testosterone, other androgens include, Dehydroepiandrosterone is a steroid hormone produced in the adrenal cortex from cholesterol. It is the precursor of natural estrogens. DHEA is also called dehydroisoandrosterone or dehydroandrosterone, androstenedione is an androgenic steroid produced by the testes, adrenal cortex, and ovaries. While androstenediones are converted metabolically to testosterone and other androgens, they are also the parent structure of estrone, use of androstenedione as an athletic or bodybuilding supplement has been banned by the International Olympic Committee, as well as other sporting organizations. Androstenediol is the steroid metabolite thought to act as the regulator of gonadotropin secretion. It is found in equal amounts in the plasma and urine of both males and females. Dihydrotestosterone is a metabolite of testosterone, and a potent androgen than testosterone in that it binds more strongly to androgen receptors. It is produced in the skin and reproductive tissue, during mammalian development, the gonads are at first capable of becoming either ovaries or testes. In humans, starting at about week 4, the rudiments are present within the intermediate mesoderm adjacent to the developing kidneys. At about week 6, epithelial sex cords develop within the forming testes, in males, certain Y chromosome genes, particularly SRY, control development of the male phenotype, including conversion of the early bipotential gonad into testes. In males, the sex cords fully invade the developing gonads, the mesoderm-derived epithelial cells of the sex cords in developing testes become the Sertoli cells, which will function to support sperm cell formation

17.
Estrogen
–
Estrogen or oestrogen is the primary female sex hormone as well as a medication. It is responsible for the development and regulation of the reproductive system. Estrogen may also refer to any substance, natural or synthetic, the estrane steroid estradiol is the most potent and prevalent endogenous estrogen, although several metabolites of estradiol also have estrogenic hormonal activity. They are one of three types of sex hormones, the others being androgens/anabolic steroids like testosterone and progestogens like progesterone, estrogens are synthesized in all vertebrates as well as some insects. Their presence in both vertebrates and insects suggests that sex hormones have an ancient evolutionary history. The three major naturally occurring forms of estrogen in women are estrone, estradiol, and estriol, another type of estrogen called estetrol is produced only during pregnancy. Quantitatively, estrogens circulate at lower levels than androgens in both men and women, while estrogen levels are significantly lower in males compared to females, estrogens nevertheless also have important physiological roles in males. Like all steroid hormones, estrogens readily diffuse across the cell membrane, once inside the cell, they bind to and activate estrogen receptors which in turn modulate the expression of many genes. Additionally, estrogens bind to and activate rapid-signaling membrane estrogen receptors, the three major naturally occurring estrogens in women are estrone, estradiol, and estriol. Estradiol is the predominant estrogen during reproductive years both in terms of serum levels as well as in terms of estrogenic activity. During menopause, estrone is the predominant circulating estrogen and during pregnancy estriol is the predominant circulating estrogen in terms of serum levels. Though estriol is the most plentiful of the three estrogens it is also the weakest, whereas estradiol is the strongest with a potency of approximately 80 times that of estriol. Thus, estradiol is the most important estrogen in non-pregnant females who are between the menarche and menopause stages of life, however, during pregnancy this role shifts to estriol, and in postmenopausal women estrone becomes the primary form of estrogen in the body. Another type of estrogen called estetrol is produced only during pregnancy, all of the different forms of estrogen are synthesized from androgens, specifically testosterone and androstenedione, by the enzyme aromatase. Estradiol, estrone, and estriol have all been approved as drugs and are used medically. Estetrol is currently under development for medical indications, but has not yet approved in any country. A variety of synthetic estrogen esters, such as estradiol valerate, estradiol cypionate, estradiol acetate, estradiol undecylate, polyestradiol phosphate, the aforementioned compounds behave as prodrugs to estradiol, and are longer-lasting in comparison. Esters of estrone and estriol also exist and are employed in clinical medicine, ethinylestradiol is a more potent synthetic analogue of estradiol that is used widely in hormonal contraceptives

18.
Glucocorticoid
–
Glucocorticoids are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the receptor, that is present in almost every vertebrate animal cell. The name glucocorticoid is composed from its role in regulation of metabolism, synthesis in the adrenal cortex. A less common synonym is glucocorticosteroid, gCs are part of the feedback mechanism in the immune system which reduces certain aspects of immune function, such as reduction of inflammation. They are therefore used in medicine to treat diseases caused by an immune system, such as allergies, asthma, autoimmune diseases. GCs have many effects, including potentially harmful side effects. They also interfere with some of the mechanisms in cancer cells. This includes, inhibitory effects on lymphocyte proliferation as in the treatment of lymphomas and leukemias, gCs affect cells by binding to the glucocorticoid receptor. Glucocorticoids are distinguished from mineralocorticoids and sex steroids by their specific receptors, target cells, in technical terms, corticosteroid refers to both glucocorticoids and mineralocorticoids, but is often used as a synonym for glucocorticoid. Glucocorticoids are chiefly produced in the zona fasciculata of the adrenal cortex, cortisol is the most important human glucocorticoid. It is essential for life, and it regulates or supports a variety of important cardiovascular, metabolic, immunologic, glucocorticoid effects may be broadly classified into two major categories, immunological and metabolic. In addition, glucocorticoids play important roles in development and body fluid homeostasis. As discussed in detail below, glucocorticoids function through interaction with the glucocorticoid receptor. Down-regulate the expression of proinflammatory proteins, glucocorticoids are also shown to play a role in the development and homeostasis of T lymphocytes. This has been shown in mice with either increased or decreased sensitivity of T cell lineage to glucocorticoids. The name glucocorticoid derives from early observations that these hormones were involved in glucose metabolism, in the fasted state, cortisol stimulates several processes that collectively serve to increase and maintain normal concentrations of glucose in blood. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best-known metabolic function of glucocorticoids, mobilization of amino acids from extrahepatic tissues, These serve as substrates for gluconeogenesis. Excessive glucocorticoid levels resulting from administration as a drug or hyperadrenocorticism have effects on many systems, some examples include inhibition of bone formation, suppression of calcium absorption, delayed wound healing, muscle weakness, and increased risk of infection

19.
Mineralocorticoid
–
Mineralocorticoids are a class of corticosteroids, which are a class of steroid hormones. Mineralocorticoids are corticosteroids that influence salt and water balances, the primary mineralocorticoid is aldosterone, notable for an aldehyde group at the 18 position. The name mineralocorticoid derives from early observations that these hormones were involved in the retention of sodium, the primary endogenous mineralocorticoid is aldosterone, although a number of other endogenous hormones have mineralocorticoid function. This in turn results in an increase of pressure and blood volume. Mineralocorticoids bind to the receptor in the cell cytosol, and are able to freely cross the lipid bilayer of the cell. This type of receptor becomes activated upon ligand binding, the opposite mechanism is called transrepression. The hormone receptor without ligand binding interacts with heat shock proteins, aldosterone and cortisol have similar affinity for the mineralocorticoid receptor, however, glucocorticoids circulate at roughly 100 times the level of mineralocorticoids. An enzyme exists in mineralocorticoid target tissues to prevent overstimulation by glucocorticoids and this enzyme, 11-beta hydroxysteroid dehydrogenase type II, catalyzes the deactivation of glucocorticoids to 11-dehydro metabolites. Licorice is known to be an inhibitor of this enzyme and chronic consumption can result in a known as pseudohyperaldosteronism. Hyperaldosteronism is commonly caused by either idiopathic adrenal hyperplasia or by an adrenal adenoma, the two main resulting problems, Hypertension and edema due to excessive Na+ and water retention. With extreme K+ loss there is muscle weakness and eventually paralysis, hypoaldosteronism leads to the salt-wasting state associated with Addisons disease, although classical congenital adrenal hyperplasia and other disease states may also cause this situation. An example of a synthetic mineralocorticoid is fludrocortisone, important antimineralocorticoids are spironolactone and eplerenone. List of corticosteroids Mineralocorticoids at the US National Library of Medicine Medical Subject Headings

20.
Neurosteroid
–
The term neurosteroid was coined by the French physiologist Étienne-Émile Baulieu and refers to steroids synthesized in the brain. The term neuroactive steroids was first coined in 1992 by Steven Paul, in addition to their actions on neuronal membrane receptors, some of these steroids may also exert effects on gene expression via nuclear steroid hormone receptors. Neurosteroids have a range of potential clinical applications from sedation to treatment of epilepsy. Ganaxolone, an analog of the endogenous neurosteroid allopregnanolone, is under investigation for the treatment of epilepsy. Based on differences in activity and structure, neurosteroids can be categorized into different groupings. The most important neurosteroids are bolded below and these neurosteroids exert inhibitory actions on neurotransmission. Androstadienol Androstadienone Androstenol Androstenone Estratetraenol Certain other endogenous steroids, such as pregnenolone, progesterone, estradiol, however, unlike those listed above, these neurosteroids do not modulate the GABAA or NMDA receptors, and instead affect various other cell surface receptors and non-genomic targets. Neurosteroids are synthesized from cholesterol, which is converted into pregnenolone, neurosteroids are produced in the brain after local synthesis or by conversion of peripherally-derived adrenal steroids or gonadal steroids. They accumulate especially in myelinating glial cells, from cholesterol or steroidal precursors imported from peripheral sources, neurosteroids also appear to play an important role in various sexually-dimorphic behaviors and emotional responses. Acute stress elevates the levels of inhibitory neurosteroids like allopregnanolone, and this is similar to the case of endorphins, which are released in response to stress and physical pain and counteract the negative subjective effects of such states. As such, it has suggested that one of the biological functions of these neuromodulators may be to help maintain emotional homeostasis. Elevated levels of inhibitory neurosteroids, namely allopregnanolone, can produce paradoxical effects, such as negative mood, anxiety, irritability, several synthetic neurosteroids have been used as sedatives for the purpose of general anaesthesia for carrying out surgical procedures. The best known of these are alphaxolone, alphadolone, hydroxydione, the first of these to be introduced was hydroxydione, which is the esterified 21-hydroxy derivative of 5β-pregnanedione. Hydroxydione proved to be a useful drug with a good safety profile. This led to the development of newer neuroactive steroids, the next drug from this family to be marketed was a mixture of alphaxolone and alphadolone, known as Althesin. This was withdrawn from use due to rare but serious toxic reactions. Neurosteroids, including ganaxolone have a spectrum of activity in animal models. They may have advantages over other GABAA receptor modulators, notably benzodiazepines, the drug continued to demonstrate efficacy in an 104-week open label extension

21.
Agonist
–
An agonist is a chemical that binds to a receptor and activates the receptor to produce a biological response. Whereas an agonist causes an action, an antagonist blocks the action of the agonist, receptors can be activated by either endogenous or exogenous agonists, resulting in a biological response. A physiological agonist is a substance that creates the same bodily responses but does not bind to the same receptor, an endogenous agonist for a particular receptor is a compound naturally produced by the body that binds to and activates that receptor. For example, the endogenous agonist for serotonin receptors is serotonin, a superagonist is a compound that is capable of producing a greater maximal response than the endogenous agonist for the target receptor, and thus has an efficacy of more than 100%. Full agonists bind and activate a receptor, producing full efficacy at that receptor, one example of a drug that acts as a full agonist is isoproterenol, which mimics the action of adrenaline at β adrenoreceptors. Another example is morphine, which mimics the actions of endorphins at μ-opioid receptors throughout the nervous system. Partial agonists also bind and activate a receptor, but have only partial efficacy at the receptor relative to a full agonist. Agents like buprenorphine are used to treat opiate dependence for this reason, as they produce milder effects on the receptor with lower dependence. An inverse agonist is an agent that binds to the same receptor binding-site as an agonist for that receptor, inverse agonists exert the opposite pharmacological effect of a receptor agonist, not merely an absence of the agonist effect as seen with antagonist. An example is the inverse agonist rimonabant. A co-agonist works with other co-agonists to produce the desired effect together, NMDA receptor activation requires the binding of both glutamate, glycine and D-serine co-agonists. An irreversible agonist is a type of agonist that binds permanently to a receptor through the formation of covalent bonds, a few of these have been described. A selective agonist is selective for a type of receptor. E. g. buspirone is a selective agonist for serotonin 5-HT1A, terms that describe this phenomenon are functional selectivity, protean agonism, or selective receptor modulators. Potency is the amount of agonist needed to elicit a desired response, the potency of an agonist is inversely related to its EC50 value. The EC50 can be measured for a given agonist by determining the concentration of agonist needed to elicit half of the biological response of the agonist. The EC50 value is useful for comparing the potency of drugs with similar efficacies producing physiologically similar effects, the smaller the EC50 value, the greater the potency of the agonist, the lower the concentration of drug that is required to elicit the maximum biological response. This relationship, termed the index, is defined as the ratio TD50, ED50

22.
Progesterone receptor
–
The progesterone receptor, also known as NR3C3 or nuclear receptor subfamily 3, group C, member 3, is a protein found inside cells. It is activated by the hormone progesterone. In humans, PR is encoded by a single PGR gene residing on chromosome 11q22, a third, lesser-known isoform, the PRC, also exists. Progesterone is necessary to induce the progesterone receptors, when no binding hormone is present the carboxyl terminal inhibits transcription. Binding to a hormone induces a change that removes the inhibitory action. Progesterone antagonists prevent the structural reconfiguration, after progesterone binds to the receptor, restructuring with dimerization follows and the complex enters the nucleus and binds to DNA. There transcription takes place, resulting in formation of messenger RNA that is translated by ribosomes to produce specific proteins. In common with other receptors, the progesterone receptor has a N-terminal regulatory domain, a DNA binding domain, a hinge section. A special transcription activation function, called TAF-3, is present in the progesterone receptor-B and this segment is not present in the receptor-A. These results suggest that in the uterus, the PR-A isoform is necessary to oppose estrogen-induced proliferation as well as PR-B-dependent proliferation, six variable sites, including four polymorphisms and five common haplotypes have been identified in the human PR gene. One promoter region polymorphism, +331G/A, creates a transcription start site. Biochemical assays showed that the +331G/A polymorphism increases transcription of the PR gene, several studies have now shown no association between progesterone receptor gene +331G/A polymorphisms and breast or endometrial cancers. However, these follow-up studies lacked the size and statistical power to make any definitive conclusions. It is currently unknown if any polymorphisms in this receptor are of significance to cancer. Knockout mice of the PR have been found to have severely impaired lobuloalveolar development of the glands as well as delayed. Progesterone receptor antagonists work as antiprogestins, selective progesterone receptor modulators may also have more or less antagonist activity. Additional PR antagonists include, onapristone, lonaprisan, APR19, EC304, WAY-255348, ORG31710, asoprisnil, telapristone, progesterone receptor has been shown to interact with, KLF9, Nuclear receptor co-repressor 2, and UBE3A

23.
Receptor antagonist
–
A receptor antagonist is a type of receptor ligand or drug that blocks or dampens agonist-mediated responses rather than provoking a biological response itself upon binding to a receptor. They are sometimes called blockers, examples include alpha blockers, beta blockers, antagonist activity may be reversible or irreversible depending on the longevity of the antagonist–receptor complex, which, in turn, depends on the nature of antagonist–receptor binding. The majority of drug antagonists achieve their potency by competing with endogenous ligands or substrates at structurally defined binding sites on receptors, biochemical receptors are large protein molecules that can be activated by the binding of a ligand. Receptors can be membrane-bound, occurring on the membrane, or intracellular. Binding occurs as a result of noncovalent interaction between the receptor and its ligand, at locations called the site on the receptor. A receptor may contain one or more binding sites for different ligands, binding to the active site on the receptor regulates receptor activation directly. The activity of receptors can also be regulated by the binding of a ligand to other sites on the receptor, antagonists mediate their effects through receptor interactions by preventing agonist-induced responses. This may be accomplished by binding to the site or the allosteric site. In addition, antagonists may interact at unique binding sites not normally involved in the regulation of the receptors activity to exert their effects. The term antagonist was originally coined to describe different profiles of drug effects, the biochemical definition of a receptor antagonist was introduced by Ariens and Stephenson in the 1950s. The current accepted definition of receptor antagonist is based on the receptor occupancy model and it narrows the definition of antagonism to consider only those compounds with opposing activities at a single receptor. Agonists were thought to turn on a cellular response by binding to the receptor. Antagonists were thought to turn off that response by blocking the receptor from the agonist and this definition also remains in use for physiological antagonists, substances that have opposing physiological actions, but act at different receptors. Our understanding of the mechanism of drug-induced receptor activation and receptor theory, the two-state model of receptor activation has given way to multistate models with intermediate conformational states. This means efficacy may actually depend on where that receptor is expressed, by definition, antagonists display no efficacy to activate the receptors they bind. Antagonists do not maintain the ability to activate a receptor, once bound, however, antagonists inhibit the function of agonists, inverse agonists, and partial agonists. In functional antagonist assays, a dose-response curve measures the effect of the ability of a range of concentrations of antagonists to reverse the activity of an agonist, the potency of an antagonist is usually defined by its half maximal inhibitory concentration IC50 value. This can be calculated for a given antagonist by determining the concentration of antagonist needed to elicit half inhibition of the biological response of an agonist

24.
Mineralocorticoid receptor
–
MR is a receptor with equal affinity for mineralocorticoids and glucocorticoids. It belongs to the nuclear receptor family where the ligand diffuses into cells, interacts with the receptor, MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system, brown adipose tissue and sweat glands. The receptor is activated by such as aldosterone and its precursor deoxycorticosterone as well as glucocorticoids. It also responds to some progestins, spironolactone and eplerenone are steroidal MR antagonists of the spirolactone group. This results in the recruitment of the transcriptional machinery and the transcription into mRNA of the DNA sequence of the activated genes. Mineralocorticoid receptor has shown to interact with, Glucocorticoid receptor. Aldosterone Glucocorticoid Mineralocorticoid Mineralocorticoid Receptors at the US National Library of Medicine Medical Subject Headings

25.
Glucocorticoid receptor
–
The glucocorticoid receptor also known as NR3C1 is the receptor to which cortisol and other glucocorticoids bind. The GR is expressed in almost every cell in the body and regulates genes controlling the development, metabolism, because the receptor gene is expressed in several forms, it has many different effects in different parts of the body. When the GR binds to glucocorticoids, its mechanism of action is the regulation of gene transcription. The unbound receptor resides in the cytosol of the cell, after the receptor is bound to glucocorticoid, the receptor-glucorticoid complex can take either of two paths. The activated GR complex up-regulates the expression of proteins in the nucleus or represses the expression of pro-inflammatory proteins in the cytosol. In humans, the GR protein is encoded by NR3C1 gene which is located on chromosome 5, the endogenous glucocorticoid hormone cortisol diffuses through the cell membrane into the cytoplasm and binds to the glucocorticoid receptor resulting in release of the heat shock proteins. The resulting activated form GR has two mechanisms of action, transactivation and transrepression, described below. This mechanism of action is referred to as transactivation, the biological response depends on the cell type. In the absence of activated GR, other factors such as NF-κB or AP-1 themselves are able to transactivate target genes. This indirect mechanism of action is referred to as transrepression, the GR is abnormal in familial glucocorticoid resistance. Dexamethasone and other corticosteroids are agonists, and mifepristone and ketoconazole are antagonists of the GR

26.
Steroidogenesis
–
A steroid is an organic compound with four rings arranged in a specific configuration. Examples include the dietary lipid cholesterol, the sex hormones estradiol and testosterone, the steroid core structure is composed of seventeen carbon atoms, bonded in four fused rings, three six-member cyclohexane rings and one five-member cyclopentane ring. Steroids vary by the groups attached to this four-ring core. Sterols are forms of steroids with a group at position three and a skeleton derived from cholestane. They can also vary more markedly by changes to the ring structure, hundreds of steroids are found in plants, animals and fungi. All steroids are manufactured in cells from the sterols lanosterol or cycloartenol, lanosterol and cycloartenol are derived from the cyclization of the triterpene squalene. The three cyclohexane rings form the skeleton of a derivative of phenanthrene. The D ring has a cyclopentane structure, when the two methyl groups and eight carbon side chains are present, the steroid is said to have a cholestane framework. The following are some categories of steroids. In eukaryotes, steroids are found in fungi, animals, animal steroids include compounds of vertebrate and insect origin, the latter including ecdysteroids such as ecdysterone. Steroid hormones include, Sex hormones, which influence sex differences and these include androgens, estrogens, and progestagens. In popular use, the term often refers to anabolic steroids. Plant steroids include steroidal alkaloids found in Solanaceae, the phytosterols, in prokaryotes, biosynthetic pathways exist for the tetracyclic steroid framework – where its origin from eukaryotes is conjectured – and the more-common pentacyclic triterpinoid hopanoid framework. One example of how MeSH performs this classification is available at the Wikipedia MeSH catalog, examples of this classification include, The gonane is the parent 17-carbon tetracyclic hydrocarbon molecule with no alkyl sidechains. Secosteroids are a subclass of steroidal compounds resulting, biosynthetically or conceptually, major secosteroid subclasses are defined by the steroid carbon atoms where this scission has taken place. Norsteroids and homosteroids are structural subclasses of steroids formed from biosynthetic steps, the former involves enzymic ring expansion-contraction reactions, and the latter is accomplished or through ring closures of acyclic precursors with more ring atoms than the parent steroid framework. Combinations of these alterations are known in nature. Ingestion of these C-nor-D-homosteroids results in defects in lambs, cyclopia from cyclopamine

27.
CYP17A1
–
It is ubiquitously expressed in many tissues and cell types, including the zona reticularis of the adrenal cortex and zona fasciculata as well as gonadal tissues. This gene encodes a member of the cytochrome P450 superfamily of enzymes and this protein localizes to the endoplasmic reticulum. It has both 17α-hydroxylase and 17, 20-lyase activities, and is a key enzyme in the pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens. The CYP17A1 gene also contains one of 27 SNPs associated with increased risk of coronary artery disease, the CYP17A1 gene resides on chromosome 10 at the band 10q24.3 and contains 8 exons. The cDNA of this gene spans a length of 1527 bp, CYP17A1 is a 57.4 kDa protein that belongs to the cytochrome P450 family. The protein encoded by its cDNA is composed of 508 amino acid residues, as an enzyme, CYP17A1 possesses an active site that associates with a heme prosthetic group to catalyze biosynthetic reactions. In addition to classical steroidogenic tissue, CYP17A1 has also detected in the heart, kidney. In the fetus, CYP17A1 has been reported in the kidney, thymus, CYP17A1 is a member of the cytochrome P450 superfamily of enzymes localized in the endoplasmic reticulum. Proteins in this family are monooxygenases that catalyze synthesis of cholesterol, steroids, CYP17A1 has both 17α-hydroxylase activity and 17, 20-lyase activity. Mutations in this gene are associated with isolated steroid-17α-hydroxylase deficiency, 17α-hydroxylase/17, 20-lyase deficiency, pseudohermaphroditism, furthermore, the 17, 20-lyase activity is dependent on cytochrome P450 oxidoreductase cytochrome b5 and phosphorylation. Cytochrome b5 acts as a facilitator for 17,20 lyase activity of CYP17A1, in humans the production of testosterone via pregnenolone to17-OHPreg and DHEA by the CYP17A1 requires POR. Human P450c17 is phosphorylated on serine and threonine residues by a cAMP-dependent protein kinase, phosphorylation of P450c17 increases 17, 20-lyase activity, while dephosphorylation virtually eliminates this activity. Mutations in this gene are associated with forms of congenital adrenal hyperplasia, specifically 17α-hydroxylase deficiency/17, 20-lyase deficiency and isolated 17. In humans, the CYP17A1 gene is associated with endocrine effects. Overall, CYP17A1 is an important target for inhibition in the treatment of cancer because it produces androgen that is required for tumor cell growth. Currently, the FDA has approved only one CYP17A1 inhibitor, abiraterone, abiraterone is structurally similar to the substrates of other cytochrome P450 enzymes involved in steroidogenesis, and interference can pose a liability in terms of side effects. Using non-steroidal scaffolds is expected to enable the design of compounds that interact more selectively with CYP17A1, potent inhibitors of the CYP17A1 enzyme provide a last line defense against ectopic androgenesis in advanced prostate cancer. The study was based on a community cohort study and four additional randomized controlled trials of primary prevention cohorts, the drug abiraterone acetate, which is used to treat castration-resistant prostate cancer, blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme

28.
Corpus luteum
–
The corpus luteum is a temporary endocrine structure in female ovaries that is involved in the production of relatively high levels of progesterone, moderate levels of estradiol and inhibin A. It is the remains of the follicle that has released a mature ovum during a previous ovulation. A new corpus luteum develops with each menstrual cycle, the corpus luteum develops from an ovarian follicle during the luteal phase of the menstrual cycle or oestrous cycle, following the release of a secondary oocyte from the follicle during ovulation. While the oocyte traverses the Fallopian tube into the uterus, the corpus luteum remains in the ovary. The corpus luteum is typically very large relative to the size of the ovary, in humans and its cells develop from the follicular cells surrounding the ovarian follicle. The follicular theca cells luteinize into small cells and follicular granulosa cells luteinize into large luteal cells forming the corpus luteum. Progesterone is synthesized from cholesterol by both the large and small luteal cells upon luteal maturation, cholesterol-LDL complexes bind to receptors on the plasma membrane of luteal cells and are internalized. Cholesterol is released and stored within the cell as cholesterol ester, LDL is recycled for further cholesterol transport. Large luteal cells produce more progesterone due to levels of protein kinase A activity within the cell. Small luteal cells have LH receptors that regulate PKA activity within the cell, PKA actively phosphorylates steroidogenic acute regulatory protein and translocator protein to transport cholesterol from the outer mitochondrial membrane to the inner mitochondrial membrane. The development of the corpus luteum is accompanied by an increase in the level of the steroidogenic enzyme P450scc that converts cholesterol to pregnenolone in the mitochondria, pregnenolone is then converted to progesterone that is secreted out of the cell and into the blood stream. The mitochondrial P450 system electron transport chain including adrenodoxin reductase and adrenodoxin has been shown to leak electrons leading to the formation of superoxide radical. Like the previous theca cells, the theca lutein cells lack the enzyme that is necessary to produce estrogen. Once the corpus luteum regresses the remnant is known as corpus albicans, the corpus luteum is essential for establishing and maintaining pregnancy in females. The corpus luteum secretes progesterone, which is a hormone responsible for the decidualization of the endometrium and maintenance. It also produces relaxin, a responsible for softening of the pubic symphysis which helps in parturition. If the egg is not fertilized, the corpus luteum stops secreting progesterone and it then degenerates into a corpus albicans, which is a mass of fibrous scar tissue. The uterine lining is expelled through the vagina, in an estrous cycle, the lining degenerates back to normal size

29.
Ovulation
–
Ovulation is the release of egg from the ovaries. In humans, this event occurs when the de Graafs follicles rupture, after ovulation, during the luteal phase, the egg will be available to be fertilized by sperm. In addition, the lining is thickened to be able to receive a fertilized egg. If no conception occurs, the lining as well as blood will be shed during menstruation. In humans, ovulation occurs about midway through the menstrual cycle, the few days surrounding ovulation, constitute the most fertile phase. In the pre-ovulatory phase of the cycle, the ovarian follicle will undergo a series of transformations called cumulus expansion. After this is done, a called the stigma will form in the follicle. Ovulation is triggered by a spike in the amount of FSH, during the luteal phase, the secondary oocyte will travel through the fallopian tubes toward the uterus. If fertilized by a sperm, the secondary oocyte or ovum may implant there 6–12 days later. The follicular phase is the phase of the cycle during which the ovarian follicles mature. The follicular phase lasts from the beginning of menstruation to the start of ovulation, for ovulation to be successful, the ovum must be supported by the corona radiata and cumulus oophorous granulosa cells. The latter undergo a period of proliferation and mucification known as cumulus expansion, mucification is the secretion of a hyaluronic acid-rich cocktail that disperses and gathers the cumulus cell network in a sticky matrix around the ovum. This network stays with the ovum after ovulation and has shown to be necessary for fertilization. An increase in cell number causes a concomitant increase in antrum fluid volume that can swell the follicle to over 20 mm in diameter. It forms a bulge at the surface of the ovary called the blister. Estrogen levels peak towards the end of the follicular phase and this causes a surge in levels of luteinizing hormone and follicle-stimulating hormone. This lasts from 24 to 36 hours, and results in the rupture of the ovarian follicles, the secondary oocyte leaves the ruptured follicle and moves out into the peritoneal cavity through the stigma, where it is caught by the fimbriae at the end of the fallopian tube. After entering the oviduct, the oocyte is pushed along by cilia, by this time, the oocyte has completed meiosis I, yielding two cells, the larger secondary oocyte that contains all of the cytoplasmic material and a smaller, inactive first polar body

30.
Luteal phase
–
The luteal phase is the latter phase of the menstrual cycle or the earlier phase of the estrous cycle. It begins with the formation of the corpus luteum and ends in either pregnancy or luteolysis, the main hormone associated with this stage is progesterone, which is significantly higher during the luteal phase than other phases of the cycle. The opposite of the phase, the rest of the two weeks, is called the follicular phase. After ovulation, the pituitary hormones FSH and LH cause the remaining parts of the dominant follicle to transform into the corpus luteum. It continues to grow for some time after ovulation and produces significant amounts of hormones, particularly progesterone, and, to a lesser extent, oestrogen. Several days after ovulation, the amount of estrogen produced by the corpus luteum may cause one or two days of fertile cervical mucus, lower basal body temperatures, or both. This is known as a secondary oestrogen surge, the hormones produced by the corpus luteum also suppress production of the FSH and LH that the corpus luteum needs to maintain itself. With continued low levels of FSH and LH, the corpus luteum will atrophy, the death of the corpus luteum results in falling levels of progesterone and oestrogen. These falling levels of ovarian hormones cause increased levels of FSH, continued drops in levels of oestrogen and progesterone trigger the end of the luteal phase, menstruation and the beginning of the next cycle. The human luteal phase lasts between ten and sixteen days, the average being fourteen days, luteal phases of less than twelve days may make it more difficult to achieve pregnancy. While luteal phase length varies significantly from woman to woman, for the woman the length will be fairly consistent from cycle to cycle. Because the hormone is unique to the embryo, most pregnancy tests look for the presence of hCG, if implantation occurs, the corpus luteum will continue to produce progesterone for eight to twelve weeks, after which the placenta takes over this function. Luteal phase defect, or luteal insufficiency, occurs when the phase is shorter than normal, progesterone levels during the luteal phase are below normal. LPD is believed to interfere with the implantation of embryos. The lactational amenorrhea method of control works primarily by preventing ovulation. There is unruptured luteinized follicle syndrome, short luteal phases that are, for example, nine days long, some people have seen normalization with a high dose of vitamin B6. ULFS can be treated by a dose of hCG at ovulation. LPD can be diagnosed by ultrasound, day 21 progesterone tests, and observing the length of luteal phase

Gas chromatography (GC) is a common type of chromatography used in analytical chemistry for separating and analyzing …

A gas chromatograph with a headspace sampler

This image above shows the interior of a GeoStrata Technologies Eclipse Gas Chromatograph that runs continuously in three-minute cycles. Two valves are used to switch the test gas into the sample loop. After filling the sample loop with test gas, the valves are switched again applying carrier gas pressure to the sample loop and forcing the sample through the column for separation.

Ovulation is the release of eggs from the ovaries. In humans, this event occurs when the follicles rupture and release …

Following a surge of luteinizing hormone (LH), an oocyte (immature egg cell) will be released into the uterine tube, where it will then be available to be fertilized by a male's sperm. Ovulation marks the end of the follicular phase of the ovarian cycle and the start of the luteal phase.

This diagram shows the hormonal changes around the time of ovulation, as well as the inter-cycle and inter-female variabilities in its timing.

Nandrolone, also known as 19-nortestosterone, is an androgen and anabolic steroid (AAS) which is used in the form of …

QV Nandrolone Deca, a form of nandrolone used by athletes.

Nandrolone, with the differences from testosterone highlighted in red. The methyl group in testosterone at the C19 position has been removed, and the C17β position is where esters are attached to nandrolone.

The Haller-Bauer reaction occurs between a non-enolizable ketone and a strong amide base. In this prototypical example involving benzophenone, the tetrahedral intermediate expels phenyl anion to give benzamide and benzene as the organic products

Dexamethasone - a synthetic glucocorticoid binds more powerfully to the glucocorticoid receptor than cortisol does. Dexamethasone is based on the cortisol structure but differs at three positions (extra double bond in the A-ring between carbons 1 and 2 and addition of a 9-α-fluoro group and a 16-α-methyl substituent).

A hydroxy or hydroxyl group is the entity with the formula OH. It contains oxygen bonded to hydrogen. In organic …

Representation of an organic hydroxy group, where R represents a hydrocarbon or other organic moiety, the red and grey spheres represent oxygen and hydrogen atoms respectively, and the rod-like connections between these, covalentchemical bonds.